Crossing borders: A systematic review with quantitative analysis of genetic mutations of carcinomas of the biliary tract

Crit Rev Oncol Hematol. 2019 Aug:140:8-16. doi: 10.1016/j.critrevonc.2019.05.011. Epub 2019 May 24.

Abstract

Biliary tract carcinoma (BTC) comprises gallbladder and intra-/extrahepatic cholangiocarcinoma (GBC, ICC, EHC), which are currently classified by anatomical origin. Better understanding of the mutational profile of BTCs might refine classification and improve treatment. We performed a systematic review of studies reporting on mutational profiling of BTC. We included articles reporting on whole-exome/whole-genome-sequencing (WES/WGS) and targeted sequencing (TS) of BTC, published between 2000-2017. Pooled mutation proportions were calculated, stratified by anatomical region and sequencing technique. A total of 25 studies with 1806 patients were included. Overall, TP53 was the most commonly mutated gene in BTC. GBC was associated with mutations in PFKFB3, PLXN2 and PGAP1. Mutations in IDH1, IDH2 and FGFR fusions almost exclusively occurred in ICC patients. Mutations in APC, GNAS and TGFBR2 occurred exclusively in EHC patients. In conclusion, subtypes of BTCs exhibit minor differences in mutational profile, which is likely influenced by the cell of origin.

Keywords: Biliary tract; Cancer biology; Cholangiocarcinoma; Genomics.

Publication types

  • Systematic Review

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Biliary Tract Neoplasms / genetics*
  • Biliary Tract Neoplasms / metabolism
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism
  • Chromogranins / genetics
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Membrane Proteins / genetics
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Phosphofructokinase-2 / genetics
  • Phosphoric Monoester Hydrolases / genetics
  • Receptor, Transforming Growth Factor-beta Type II / genetics

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Chromogranins
  • Membrane Proteins
  • Neoplasm Proteins
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • PFKFB3 protein, human
  • Phosphofructokinase-2
  • Receptor, Transforming Growth Factor-beta Type II
  • TGFBR2 protein, human
  • PGAP1 protein, human
  • Phosphoric Monoester Hydrolases
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs